Bile pigment phamacokinetics and absorption in the rat: Therapeutic potential for enteral administration

Bulmer, A. C., Coombes, J. S., Blanchfield, J. T., Toth, I., Fassett, R. G. and Taylor, S. M. (2011) Bile pigment phamacokinetics and absorption in the rat: Therapeutic potential for enteral administration. British Journal of Pharmacology, 164 7: 1857-1870.


Author Bulmer, A. C.
Coombes, J. S.
Blanchfield, J. T.
Toth, I.
Fassett, R. G.
Taylor, S. M.
Title Bile pigment phamacokinetics and absorption in the rat: Therapeutic potential for enteral administration
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
1476-5381
Publication date 2011-12
Sub-type Article (original research)
DOI 10.1111/j.1476-5381.2011.01413.x
Volume 164
Issue 7
Start page 1857
End page 1870
Total pages 14
Place of publication Chichester, West Sussex, U.K.
Publisher John Wiley & Sons
Collection year 2012
Language eng
Formatted abstract BACKGROUND AND PURPOSE Bilirubin and biliverdin possess antioxidant and anti-inflammatory properties and their exogenous administration protects against the effects of inflammation and trauma in experimental models. Despite the therapeutic potential of bile pigments, little is known about their in vivo parenteral or enteral absorption after exogenous administration. This study investigated the absorption and pharmacokinetics of bile pigments after i.v., i.p. and intraduodenal (i.d.) administration in addition to their metabolism and routes of excretion.

EXPERIMENTAL APPROACH
Anaesthetized Wistar rats had their bile duct, jugular and portal veins cannulated. Bile pigments were infused and their circulating concentrations/biliary excretion were measured over 180 min.

KEY RESULTS
After i.v. administration of unconjugated bilirubin, biliverdin and bilirubin ditaurate, their plasma concentrations decreased exponentially over time. Subsequently, native and metabolized compounds appeared in the bile. When administered i.p., their absolute bioavailabilities equalled 14.0, 16.1 and 33.1%, respectively, and correspondingly 38, 28 and 34% of the same bile pigment doses were excreted in the bile. Administration of unconjugated bilirubin and bilirubin ditaurate i.d. increased their portal and systemic concentrations and their systemic bioavailability equalled 1.0 and 2.0%, respectively. Correspondingly, 2.7 and 4.6%, of the doses were excreted in the bile. Biliverdin was rapidly metabolized and these products were absorbed and excreted via the urine and bile.

CONCLUSIONS AND IMPLICATIONS
Bile pigment absorption from the peritoneal and duodenal cavities demonstrate new routes of administration for the treatment of inflammatory and traumatic pathology. Oral biliverdin administration may lead to the production of active metabolite that protect from inflammation/complement activation.
Keyword Bile pigment
Administration
Kinetics
Half-life
Metabolism
Excretion
Inflammation
Oxidative stress
Antioxidant
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Special Issue: Themed Section: Transporters. Guest Editor: Steve Alexander

 
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Created: Fri, 30 Sep 2011, 12:49:50 EST by Matthew Lamb on behalf of School of Medicine